Heartland CardiologyHeartland Cardiology

Dr. John DongasDr. John Dongas

The Beat Goes On: The Beat Goes On: Biventricular Biventricular

DevicesDevices

DisclosuresDisclosures

• I have nothing to discloseI have nothing to disclose

AgendaAgenda

• Sudden Cardiac Death (SCD) and Sudden Cardiac Death (SCD) and related clinical trialsrelated clinical trials

• Cardiac Resynchronization Therapy Cardiac Resynchronization Therapy (CRT) and related clinical trials(CRT) and related clinical trials

•Approximately Approximately 460,000460,000 people yearly will people yearly will die of Sudden Cardiac Deathdie of Sudden Cardiac Death

•Other causesOther causes– StrokeStroke22 160,000160,000– Lung cancerLung cancer33 90,100 90,100– Breast cancerBreast cancer33 40,200 40,200– Automobile accidentAutomobile accident44 50,000 50,000– AIDSAIDS55 16,000 16,000– FiresFires66 4,000 4,000

4National Transportation Safety Board, 2000.5Center for Disease Control, 2001.6NFPA, U.S. Facts & Figures, 2000.

Sudden Cardiac Death Sudden Cardiac Death in the USin the US

1NASPE, May 2000.2American Heart Association, 2000.3National Cancer Institute, 2001.

Presented by John D. Day, MD, University of Utah Medical Center, September 2003, Las Vegas, NV

Odds of Surviving Sudden Cardiac Death

•Overall:

•New York City or Chicago:

•Seattle:

•Hospital:

•American Airlines in Flight:

•Las Vegas Casino:

40%

40%

70%

30%

1%

5%

•There is a large and growing body of There is a large and growing body of scientific evidence demonstrating the scientific evidence demonstrating the benefits of both pharmacological and device benefits of both pharmacological and device therapies for patients with Left Ventricular therapies for patients with Left Ventricular Dysfunction who are at risk for SCDDysfunction who are at risk for SCD– MADITMADIT 19961996 n = 196n = 196– MUSTT MUSTT 19991999 n = 704n = 704– MADIT II MADIT II 20022002 n = 1,232n = 1,232 N = 6,173 N = 6,173– COMPANION COMPANION 20032003 n = 1,520n = 1,520– SCD-HeFT SCD-HeFT 20042004 n = 2,521n = 2,521

Clinical OverviewClinical Overview

MADIT II Trial DesignMADIT II Trial Design

• PopulationPopulation

• 1,232 patients with:1,232 patients with:– Prior MI (> 1 month before enrollment)Prior MI (> 1 month before enrollment)– EF EF 30% 30%– No arrhythmia markers were No arrhythmia markers were

required for inclusion in MADIT IIrequired for inclusion in MADIT II– Medication in treatment arms was Medication in treatment arms was

similarsimilar

MADIT II Trial DesignMADIT II Trial Design• Prospective, multicenter, Prospective, multicenter,

randomized designrandomized design

• Primary endpoint: All cause Primary endpoint: All cause mortalitymortality

Eligible patients

Noninvasive evaluation of LV function

Randomization

ICD+OPT (n=742) OPT (n=490)

Average 20-month follow-up including OPT

MADIT II: Addition of an ICD MADIT II: Addition of an ICD Improves SurvivalImproves Survival

Moss AJ, et al. N Engl J Med 2002;346:877-883. (Permission for use requested)

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Years

• 31% relative reduction in all-cause mortality at average 20 month follow-up

• 5.6% absolute reduction in all-cause mortality at average 20-month follow-up

ICD + OPT groupOPT group

Medicare ICD Approved Medicare ICD Approved IndicationsIndications

• -Prior MI (>1 month) and -Prior MI (>1 month) and

• -EF< 30%-EF< 30%

1American Heart Association. 2002 heart and stroke statistical update. American Heart Association, 2001.2MERIT-HF study group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL randomized intervention trial in congestive heart failure (MERIT-HF). LANCET. 1999;353:2001-07.

Sudden cardiac death Sudden cardiac death (SCD)(SCD)

High risk in heart failure patientsHigh risk in heart failure patients– Heart failure patients experience SCD at six to Heart failure patients experience SCD at six to

nine times the rate of the general populationnine times the rate of the general population11

– Sudden death is the predominant mode of death Sudden death is the predominant mode of death in mild to moderate heart failurein mild to moderate heart failure22

SCD-HeFTSCD-HeFT

The Sudden Cardiac Death The Sudden Cardiac Death in Heart Failure Trial: SCD-in Heart Failure Trial: SCD-HeFTHeFT

•Design:Design:– Prospective, Multi-center, RandomizedProspective, Multi-center, Randomized– 2521 Patients enrolled2521 Patients enrolled

•Inclusion Criteria:Inclusion Criteria:– NYHA class II/III Heart Failure due to ischemic or non-NYHA class II/III Heart Failure due to ischemic or non-

ischemic dilated cardiomyopathyischemic dilated cardiomyopathy– EF EF 35% 35%– CHF CHF 3 months 3 months– Age Age 18 years 18 years– CHF treatment with vasodilatorsCHF treatment with vasodilators– No cardiac arrest or episode of sustained VTNo cardiac arrest or episode of sustained VT

Bardy GH, et al. N Engl J Med. 2005;352:225-237

SCD-HeFT: Tested ICDs or SCD-HeFT: Tested ICDs or Amiodarone on Top of Amiodarone on Top of Conventional Therapy (CT)Conventional Therapy (CT)

Bardy GH, et al. N Engl J Med. 2005;352:225-237

Eligible Patients

Electrocardiography, Liver & Thyroid function tests, Six Minute Walk, Holter Monitor and Chest Radiography

Randomization

1 Patient 1 Patient 1 Patient Conventional Therapy CT + Amiodarone CT + ICD

SCD-HeFT: ConclusionsSCD-HeFT: Conclusions

• In class II or III HF patients with EF In class II or III HF patients with EF << 35% on good background drug therapy, 35% on good background drug therapy, the mortality rate for placebo-controlled the mortality rate for placebo-controlled patients is 7.2% per year over 5 yearspatients is 7.2% per year over 5 years

• ICD's decrease mortality by 23%ICD's decrease mortality by 23%

• Amiodarone, when used as a primary Amiodarone, when used as a primary preventive agent, does not improve preventive agent, does not improve survivalsurvival

Myocardial InfactionMyocardial Infaction

Ejection FractionEjection Fraction

Ventricular FibrillationVentricular Fibrillation

Synchronny vs. Synchronny vs. Dysynchronny in HFDysynchronny in HF

Comparison of medical therapy, pacing Comparison of medical therapy, pacing and defibrillation in HF: COMPANIONand defibrillation in HF: COMPANION

• Design Design – Open-labelOpen-label– Prospective Prospective – Multicenter Multicenter – RandomizedRandomized– Parallel Parallel

• ObjectiveObjective– Compare OPT alone vs Compare OPT alone vs

OPT with CRT/ICD vs OPT with CRT/ICD vs OPT with CRT aloneOPT with CRT alone

• 128 centers across the US 128 centers across the US

Bristow MR, et al. N Engl J Med. 2004;350:2140-2150

COMPANION: Key eligibility COMPANION: Key eligibility criteriacriteria

• NYHA Class III or IVNYHA Class III or IV

• NSR, QRS NSR, QRS 120 ms, PR interval >150ms 120 ms, PR interval >150ms

• LVEF LVEF 35%, LVEDD 35%, LVEDD 60 mm60 mm

• Optimal pharmacological therapyOptimal pharmacological therapy– Beta blocker (for at least 3 months)Beta blocker (for at least 3 months)– Diuretic, ACEI/ARB, spironolactone (1 month), Diuretic, ACEI/ARB, spironolactone (1 month),

+/- digoxin+/- digoxin

• History of HF hospitalization (or pharmacologic History of HF hospitalization (or pharmacologic equivalent) equivalent)

• <12 months, >1 month prior to enrollment<12 months, >1 month prior to enrollment

• No indication for bradycardia or tachyarrhythmia No indication for bradycardia or tachyarrhythmia device at the time of enrollmentdevice at the time of enrollment

Bristow MR, et al. N Engl J Med. 2004;350:2140-2150

Courtesy of C. Stellbrink, MD.

Healthy DCM - Intrinsic

Issues associated with Issues associated with heart failureheart failure

Abnormal wall motionAbnormal wall motion

Click for animations

ConclusionsConclusions

When added to optimal pharmacological therapy in patients with moderate to severe LV dysfunction, NYHA Class III or IV symptoms and QRS lengthening:

• CRT or CRT-D reduce mortality and first hospitalization*

• CRT-D reduces mortality

2/3 of the reduction is attributed to CRT

Bristow MR, et al. N Engl J Med. 2004;350:2140-2150

* Hospitalization– Care provided at a hospital for any reason over a time period that involves a date change– In-patient or out-patient use of IV inotropes and/or vasoactive drugs for more than 4 hours– Hospitalizations associated with a device implant attempt or re-attempt are excluded

COMPANION – Primary COMPANION – Primary EndpointEndpoint

~19% reduction with CRT~20% reduction with CRT-D

Secondary Endpoint – Secondary Endpoint – All cause mortalityAll cause mortality

~24% reduction with CRT~36% reduction with CRT-D

COMPANION COMPANION ConclusionsConclusions

When added to optimal pharmacological therapy inpatients with moderate-severe LV dysfunction, NYHAClass III or IV symptoms and QRS lengthening:

•CRT or CRT-D reduces mortality + hospitalizations

•CRT-D reduced the relative risk of mortality by 36%

• Intraventricular Activation • Organized ventricular

activation sequence• Coordinated septal and

free-wall contraction• Improved pumping

efficiency

Issues associated with Issues associated with heart failureheart failure

Mechanism II–ventricular resynchronizationMechanism II–ventricular resynchronization

Sinus node

AVnode

Stimulation therapy

Conduction block

Resynchronization Resynchronization TherapyTherapy

• Patients who are at high risk of sudden cardiac death due to ventricular arrhythmias

• Moderate to severe heart failure, NYHA Class III/IV• Left ventricular dysfunction, EF 35%• QRS duration 120 ms and • Symptomatic despite stable, optimal heart failure

drug therapy

FDA Indications

CRT-D Indications

Baseline DCM with CRT

Courtesy of C. Stellbrink, MD.

Issues associated with Issues associated with heart failureheart failure

Cardiac resynchronization therapy (CRT)Cardiac resynchronization therapy (CRT)– global synchrony– global synchrony

Click for animations

Revised ACC/AHA Revised ACC/AHA Guidelines impact ICD and Guidelines impact ICD and CRT TherapiesCRT Therapies

The New Standard of Care

The American College of Cardiology (ACC) and American Heart Association (AHA) have just announced they have incorporated revised treatment recommendations for ICD and CRT therapies into the heart failure guidelines. ICD and CRT therapies are now Class I for many patients who are indicated under the MADIT II and COMPANION trials(1).

(1) http://www.acc.org/clinical/guidelines/failure/index.pdf

ACC/AHA Guidelines ACC/AHA Guidelines FormatFormat

Class I: Conditions for which there is evidence and/or general agreement that a given procedure or treatment is beneficial, useful, and effective.Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment.

Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy.

Class IIb: Usefulness/efficacy is less well established by evidence/opinion.

Class III: Conditions for which there is evidence and/or general agreement that a procedure/treatment is not useful/effective and in some cases may be harmful.

SummarySummary

– ICD and CRT therapies ICD and CRT therapies are the standards of are the standards of care recognized by the care recognized by the ACC and AHAACC and AHA